Zhang Qian, Cheng Fang, Zhang Zhaojian, Wang Bing, Zhang Xiaobao
Department of Anesthesiology, The First People's Hospital of Lianyungang, 182 Tongguan Road, Lianyungang 222000, Jiangsu, China.
Department of Anesthesiology, Lianyungang Oriental Hospital, Lianyungang, Jiangsu, China.
Life Sci. 2021 Jan 27:119042. doi: 10.1016/j.lfs.2021.119042.
Lung cancer is a common malignant tumor around the world. Propofol has been found to play an anti-tumor role. Therefore, the purpose of this study is to clarify the role and underlying molecular mechanisms of Propofol in non-small cell lung cancer (NSCLC).
The real-time quantitative polymerase chain reaction (RT-qPCR) assay was conducted to measure the expression levels of circular_RHOT1 (circ-RHOT1), microRNA (miR)-326, and Forkhead Box M1 (FOXM1) in tissues and cells. The proliferation of cell was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT) and colony forming assays. The flow cytometry assay was used to evaluate cell apoptosis. The migration and invasion of NSCLC cells were determined by transwell assay. The protein expression level of FOXM1 was quantified by western blot assay. The association between miR-326 and circ-RHOT1 or FOXM1 was confirmed by dual-luciferase reporter assay.
Circ-RHOT1 was increased in NSCLC tissues and cells. Importantly, treatment with Propofol inhibited circ-RHOT1 expression in NSCLC cells. Propofol dose-dependently inhibited proliferation, migration and invasion while induced apoptosis of NSCLC cells, which was abolished by circ-RHOT1 overexpression, FOXM1 overexpression, or miR-326 silencing. MiR-326, interacted with FOXM1, was a target of circ-RHOT1 in NSCLC cells, which was confirmed by dual-luciferase reporter assay. Circ-RHOT1 regulated FOXM1 expression by sponging miR-326 in NSCLC cells. In addition, inhibition of circ-RHOT1 in combined with Propofol impeded tumorigenesis in vivo.
Propofol repressed proliferation, migration and invasion while induced apoptosis of NSCLC cells at least in part by regulation of circ-RHOT1/miR-326/FOXM1 axis in NSCLC cells.
肺癌是全球常见的恶性肿瘤。已发现丙泊酚具有抗肿瘤作用。因此，本研究旨在阐明丙泊酚在非小细胞肺癌（NSCLC）中的作用及潜在分子机制。
采用实时定量聚合酶链反应（RT-qPCR）检测组织和细胞中环状_RHOT1（circ-RHOT1）、微小RNA（miR）-326和叉头框M1（FOXM1）的表达水平。通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-2H-四唑溴盐（MTT）和集落形成试验测定细胞增殖。采用流式细胞术检测细胞凋亡。通过Transwell试验测定NSCLC细胞的迁移和侵袭能力。采用蛋白质免疫印迹法检测FOXM1蛋白表达水平。通过双荧光素酶报告基因试验证实miR-326与circ-RHOT1或FOXM1之间的关联。
circ-RHOT1在NSCLC组织和细胞中表达升高。重要的是，丙泊酚处理可抑制NSCLC细胞中circ-RHOT1的表达。丙泊酚剂量依赖性地抑制NSCLC细胞的增殖、迁移和侵袭，同时诱导其凋亡，而circ-RHOT1过表达、FOXM1过表达或miR-326沉默可消除这种作用。双荧光素酶报告基因试验证实，miR-326与FOXM1相互作用，是NSCLC细胞中circ-RHOT1的靶点。在NSCLC细胞中，circ-RHOT1通过吸附miR-326来调节FOXM1的表达。此外，抑制circ-RHOT1并联合丙泊酚可抑制体内肿瘤发生。
丙泊酚至少部分通过调节NSCLC细胞中的circ-RHOT1/miR-326/FOXM1轴来抑制NSCLC细胞的增殖、迁移和侵袭，并诱导其凋亡。
